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dc.contributor.authorPender, M
dc.contributor.authorHodgkinson, S
dc.contributor.authorBroadley, S
dc.contributor.authorLindsey, J
dc.contributor.authorIoannides, Z
dc.contributor.authorMunson, D
dc.contributor.authorRasor, K
dc.contributor.authorForozan, F
dc.contributor.authorFoubert, P
dc.contributor.authorAftab, B
dc.contributor.authorGamelin, L
dc.contributor.authorYe, W
dc.contributor.authorWillmer, J
dc.date.accessioned2020-04-07T05:25:24Z
dc.date.available2020-04-07T05:25:24Z
dc.date.issued2019
dc.identifier.issn1352-4585
dc.identifier.doi10.1177/1352458519869496
dc.identifier.urihttp://hdl.handle.net/10072/393017
dc.description.abstractIntroduction: Evidence suggests Epstein-Barr virus (EBV) infection is associated with multiple sclerosis pathogenesis. In patients (pt) with progressive forms of MS (pMS), autologous EBV-specific T cells may prevent progression and improve symptoms (Pender, et al. JCI Insight. 2018). Objectives: To evaluate ATA188, an off-the-shelf, allogeneic, EBV-targeted T cell immunotherapy comprised of HLA-matched, in vitro-expanded, cytotoxic T lymphocytes in a first-in-human, multicenter, 2-part study in adults with pMS (NCT03283826). Preliminary data are reported. Methods: Eligible pt (age 18–< 66) are EBV-seropositive with pMS and an Expanded Disability Status Scale (EDSS) score of 3–7. Cohorts (cht) 1–4 (6–9 pt/cht) receive escalating doses of ATA188. 1° endpoints: safety and identification of the recommended phase 2 dose (RP2D) of ATA188. Efficacy criteria: EDSS, MS Impact Scale-29, Fatigue Severity Scale, and 12-Item MS Walking Scale scores; timed 25-foot walk; 9-hole Peg Test; and visual acuity. A responder (R) has sustained ⩾ minimal clinically significant (MCS) improvement from BL in 2 consecutive evaluations on ⩾2 efficacy criteria; a partial responder (PR) has ⩾ MCS improvement from baseline (BL) in any 1 evaluation on ⩾2 efficacy criteria; and a non-responder (NR) has ⩾ MCS decline from BL in any 1 evaluation on ⩾2 efficacy criteria (if both criteria are met, pt is NR). Plasma inflammatory biomarkers (IL-2, IL-1β, TNF-α, IL-6) are monitored throughout treatment. Results: As of 27 May 2019, 19 pt (53% male; median age, 56 years) have enrolled (6 in each of cht 1–3; 1 in cht 4) and received ⩾1 dose of ATA188. Treatment-emergent AEs (TEAE) occurred in 63% (12/19) pt and treatment-related AEs (TRAE) in 37% (7/19) pt; 1 pt (cht 2) had a grade ⩾ 3 TEAE, and 1 (cht 4) had a serious TRAE. No dose-limiting toxicities or fatal TEAE have been reported. Efficacy data are available for cht 1 and 2: cht 1, 1 R, 1 PR, and 4 NR at 6 months and 1 R, 0 PR, and 1 NR at 12 months; cht 2, 2 R, 4 PR, and 0 NR at 6 months. On measures of disability, 3/6 showed improvement and 3/6 showed decline in cht 1; 4/6 showed improvement and 1/6 showed decline in cht 2. Inflammatory cytokines remained at or near baseline. Conclusion: Preliminary data indicate ATA188 is well tolerated and improves efficacy measures in adults with pMS, even at lower doses. These results support continuing part 1 to identify RP2D for part 2, (randomized, double-blind, placebo-controlled portion).
dc.languageEnglish
dc.publisherSage Publications Ltd
dc.relation.ispartofconferencename35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) / 24th Annual Conference of Rehabilitation in MS
dc.relation.ispartofconferencetitleMultiple Sclerosis Journal
dc.relation.ispartofdatefrom2019-09-11
dc.relation.ispartofdateto2019-09-13
dc.relation.ispartoflocationStockholm, Sweden
dc.relation.ispartofpagefrom931
dc.relation.ispartofpageto932
dc.relation.ispartofissue2_suppl
dc.relation.ispartofvolume25
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchNeurosciences
dc.subject.fieldofresearchcode3202
dc.subject.fieldofresearchcode3209
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsClinical Neurology
dc.subject.keywordsNeurosciences & Neurology
dc.titlePreliminary safety and efficacy of ATA188, a pre-manufactured, unrelated donor (off-the-shelf, allogeneic) Epstein-Barr virus-targeted T-cell immunotherapy for patients with progressive forms of multiple sclerosis
dc.typeConference output
dc.type.descriptionE3 - Conferences (Extract Paper)
dcterms.bibliographicCitationPender, M; Hodgkinson, S; Broadley, S; Lindsey, J; Ioannides, Z; Munson, D; Rasor, K; Forozan, F; Foubert, P; Aftab, B; Gamelin, L; Ye, W; Willmer, J, Preliminary safety and efficacy of ATA188, a pre-manufactured, unrelated donor (off-the-shelf, allogeneic) Epstein-Barr virus-targeted T-cell immunotherapy for patients with progressive forms of multiple sclerosis, Multiple Sclerosis Journal, 2019, 25, pp. 931-932
dc.date.updated2020-04-07T05:22:48Z
gro.hasfulltextNo Full Text
gro.griffith.authorBroadley, Simon


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